Matthew R Wolff, MD

Position title: Professor of Medicine (CHS)

Phone: 608-590-5447

Organ System/Disease Focus: Cardiovascular Disease, with a focus on the genetic and molecular basis of genetic dilated cardiomyopathys

I am a cardiovascular clinician-scientist and a cardiac patient, having undergone a combined heart and kidney transplant in 2020 for a familial (genetic) dilated cardiomyopathy resulting from a mutation in the LMNA gene. My current research focuses primarily on pre-clinical studies of novel therapeutics for LMNA-associated familial dilated cardiomyopathy, employing the murine double knock-in model of my own mutation (lmnaN195K/N195), which faithfully recapitulates the human disease as well as induced pluripotent stem cell-derived cardiomyocytes carrying the N195K mutation (differentiated from my own induced pluripotent stem cells). We are currently exploring the role of impaired autophagy in the pathogenesis of cardiac dysfunction accompanying these mutations, and developing novel autophagy agonists as potential therapies for this aggressive form of heart failure that responds poorly to conventional therapy.

Selected References:

• Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J, Humberto J, Spudich VS, Girolami UD, Seidman JG, Seidman CE. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med 1999;341:1715-24.
• Markandeya YS, Tsubouchi T, Hacker TA, Wolff MR, Belardinelli L, Balijepalli RC. Inhibition of late sodium current attenutates ionic arrhythmia mechanism in ventricular myocytes expressing LaminA-N195K mutation. Heart Rhythm 2016; 13(11):2228-2236.
• Wolff MR, Whitesell LF, Moss RL. Calcium sensitivity of isometric tension is increased in experimental heart failure. Circ Res 1995;76:781-89
• Wolff MR, Buck SH, Stoker SW, Greaser ML, Mentzer RM. Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation. J Clin Invest 1996;98:167-76
• Jiang MT, Lokuta AJ, Farrell EF, Wolff MR, Haworth RA. Valdivia HH. Abnormal Ca2+ release, but normal ryanodine receptors, in canine and human heart failure. Circ Res 2002;91:1015-22